Meng Tianjiao, Fei Qinwen, Zhu Jingying, Gu Jiayi, Li Weiyu, Wu Xianhong, Pan Gonghua, Lv Tian, Chen Shiqin
Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, China.
Department of Geriatrics, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, China.
Front Neurosci. 2024 Aug 1;18:1416431. doi: 10.3389/fnins.2024.1416431. eCollection 2024.
The effects of heart failure (HF) on cortical brain structure remain unclear. Therefore, the present study aimed to investigate the causal effects of heart failure on cortical structures in the brain using Mendelian randomization (MR) analysis.
We conducted a two-sample MR analysis utilizing genetically-predicted HF trait, left ventricular ejection fraction (LVEF), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels to examine their effects on the cortical surface area (SA) and thickness (TH) across 34 cortical brain regions. Genome-wide association study summary data were extracted from studies by Rasooly (1,266,315 participants) for HF trait, Schmidt (36,548 participants) for LVEF, the SCALLOP consortium (21,758 participants) for NT-proBNP, and the ENIGMA Consortium (51,665 participants) for cortical SA and TH. A series of MR analyses were employed to exclude heterogeneity and pleiotropy, ensuring the stability of the results. Given the exploratory nature of the study, -values between 1.22E-04 and 0.05 were considered suggestive of association, and -values below 1.22E-04 were defined as statistically significant.
In this study, we found no significant association between HF and cortical TH or SA (all > 1.22E-04). We found that the HF trait and elevated NT-proBNP levels were not associated with cortical SA, but were suggested to decrease cortical TH in the pars orbitalis, lateral orbitofrontal cortex, temporal pole, lingual gyrus, precuneus, and supramarginal gyrus. Reduced LVEF was primarily suggested to decrease cortical SA in the isthmus cingulate gyrus, frontal pole, postcentral gyrus, cuneus, and rostral middle frontal gyrus, as well as TH in the postcentral gyrus. However, it was suggested to causally increase in the SA of the posterior cingulate gyrus and medial orbitofrontal cortex and the TH of the entorhinal cortex and superior temporal gyrus.
We found 15 brain regions potentially affected by HF, which may lead to impairments in cognition, emotion, perception, memory, language, sensory processing, vision, and executive control in HF patients.
心力衰竭（HF）对大脑皮质结构的影响尚不清楚。因此，本研究旨在使用孟德尔随机化（MR）分析来探究心力衰竭对大脑皮质结构的因果效应。
我们进行了一项两样本MR分析，利用基因预测的HF特征、左心室射血分数（LVEF）和N末端脑钠肽前体（NT-proBNP）水平，来检验它们对34个大脑皮质区域的皮质表面积（SA）和厚度（TH）的影响。全基因组关联研究汇总数据分别从Rasooly的研究（1,266,315名参与者）中提取HF特征数据、Schmidt的研究（36,548名参与者）中提取LVEF数据、SCALLOP联盟（21,758名参与者）中提取NT-proBNP数据，以及ENIGMA联盟（51,665名参与者）中提取皮质SA和TH数据。采用了一系列MR分析来排除异质性和多效性，以确保结果的稳定性。鉴于本研究的探索性质，1.22E-04至0.05之间的P值被认为提示存在关联，低于1.22E-04的P值被定义为具有统计学意义。
在本研究中，我们发现HF与皮质TH或SA之间无显著关联（所有P值均>1.22E-04）。我们发现HF特征和升高的NT-proBNP水平与皮质SA无关，但提示会降低眶部、外侧眶额皮质、颞极、舌回、楔前叶和缘上回的皮质TH。LVEF降低主要提示会减少扣带峡、额极、中央后回、楔叶和额中回中部的皮质SA，以及中央后回的TH。然而，提示LVEF降低会导致后扣带回和内侧眶额皮质的SA以及内嗅皮质和颞上回的TH因果性增加。
我们发现15个脑区可能受HF影响，这可能导致HF患者在认知、情感、感知、记忆、语言、感觉处理、视觉和执行控制方面出现损害。
